Developmental Neuroscience Commons^™

Optimizing Itpa R178c Assays Via Hplc, Jared J. Reisnouer, Wally D. Pines

2026 Symposium

Two of the major nucleotide bases in DNA and RNA (Adenine and Guanine) are derived from the purine Inosine Monophosphate (IMP). IMP may occasionally form the noncanonical nucleotide Inosine Triphosphate (ITP) within the cell and become incorporated into DNA during replication, leading to potentially lethal errors. To combat this, human cells produce the “housekeeping” enzyme Inosine Triphosphatase (ITPA) to revert ITP to IMP. A mutation of this protein that replaces the 178th amino acid Arginine with Cysteine (R178C) is associated with a fatal infantile encephalopathy. Previous assessments of enzyme-substrate binding and catalysis for ITPA variants have been run at a …

Epigenetic Mechanisms For Mediating The Transmission Of Prenatal Maternal Stress And Associated Neurodevelopmental Outcomes, Kaylee Vis

Senior Honors Theses

The hypothalamic-pituitary-adrenal (HPA) axis is the primary stress response system responsible for regulating cortisol release. During pregnancy, maternal stress can dysregulate the HPA axis, leading to elevated cortisol and corticosterone levels that impact fetal development. Excessive prenatal exposure to stress has been associated with alterations in fetal brain structure and function, increasing the risk for neurodevelopmental disorders such as autism spectrum disorder, attention-deficit/hyperactivity disorder, and anxiety. Emerging research supports the idea that these neurodevelopmental effects may be transmitted through epigenetic mechanisms. However, a gap remains in the literature regarding the specific mechanism of interaction between environmental stressors, heritable epigenetic information, …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

Characterizing Border Associated Macrophages During Spinal Cord Regeneration, Addison Vogt, Dana Shaw, Mayssa Mokalled

Undergraduate Research Symposium

The human central nervous system has limited regenerative ability, with injuries to the spinal cord (SC) often resulting in paralysis. Alternatively, zebrafish have enhanced innate regenerative capacity and regain full motor function following spinal cord injury (SCI). Immune activation following SCI is necessary to provide a permissive environment for tissue repair, but the immune pathways necessary for SC regeneration are not well characterized. In previous data, we have found that while immune activation is persistent into the chronic phases of SCI response in mammals, zebrafish achieve full immune clearance within 48 days post SCI. We hypothesize that one key distinction …

Genomic Data Science Approaches For Understanding Human Diseases, Snehal Shah

All Dissertations

The intricate interplay of genetic predisposition, environmental influences, and lifestyle acts as the multifactorial landscape of diseases. Understanding this complexity presents a significant challenge. Molecular insights into disease mechanisms, particularly the interactions of DNA, RNA, and proteins with environmental and lifestyle factors, have revolutionized disease diagnosis, prognosis, and treatment. High-throughput technologies, such as next-generation sequencing, generate large amounts of molecular data, holding a wealth of knowledge. These datasets unveil the roles of genes and their interactions with various factors through analysis, shedding light on previously unknown molecular mechanisms underlying disease pathogenesis. Furthermore, they facilitate the discovery of biomarkers crucial for …

Towards Understanding The Function Of An Ets-Like Gene In Nematostella Vectensis: Generation Of A Knockout Mutant Line And A Transgenic Reporter Line, Emily Bullock

Biological Sciences Undergraduate Honors Theses

Due to their unique phylogenic position as sister to Bilateria, Cnidaria are often credited with the utility of allowing for reconstruction of ancestral biology based on characteristics shared with bilaterians and other animals. This factor makes investigation into the nervous systems of cnidarians critical in understanding early neural evolution. Wamides, a class of neuropeptides, have been shown to play a regulatory role in life cycle transitions across many different species. The cnidarian specific Wamide neuropeptide, GLWamide, has previously been identified to play an accelerator role in the metamorphic timing of a specific species of sea anemone, Nematostella vectensis. However, …

Transcriptional Regulation Of Stem Cell Function In The Drosophila Central Nervous System, Amalia S. Parra

Biology ETDs

Development of multicellular organisms depends on coordination of various molecular mechanisms to ensure proper tissue size and structure. This is accomplished through intrinsic and extrinsic cues that regulate cell growth and proliferation both spatially and temporally. These well-coordinated signals are present from early developmental stages and remain active throughout development to ensure tissue structure is appropriate for function. This is particularly important in early cell types that form specialized lineages such as stem cells or those found throughout the body such as epithelia. While much progress has been made in understanding growth regulatory mechanisms, several fundamental aspects remain unknown. This …

The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver

MUSC Theses and Dissertations

Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …

Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar

Dissertations and Theses (Open Access)

The Mediator complex (MED) is a multi-subunit protein complex integral to the eukaryotic transcription machinery. MED12 is a Cdk8- regulatory kinase module subunit directly implicated in human disease and is genetically altered in neurological disease and cancer. Numerous attempts at generating an in vivo system to study the role of Med12 failed due to embryonic lethality associated with germline or developmental disruption of Med12 gene. To understand the cellular and molecular processes associated with its role in disease, we generated multiple mouse models with targeted depletion of MED12 in distinct cellular lineages. Our genetically engineered models with induced and conditional …

Examining Development And Function Of Pretectal Visual Neural Circuits In Gs Homeobox 1 Mutant Zebrafish, Alexandra Rose Schmidt

Graduate Theses, Dissertations, and Problem Reports (ETD)

Brain development requires a coordinated genetic code to regulate initial cell identity determination, migration, and connectivity, to establish function of neural circuits. Independent neural circuits underlie our ability to produce both complex and innate behavioral responses to sensory stimuli that are often conserved across vertebrate organisms. Sensory processing disruptions are associated with several neurodevelopmental disorders (NDDs). Therefore, gene mutations altering neurodevelopment can lead to changes influencing structure and function of individual neural circuits, causing behavioral deviations in sensory responsiveness. Crucial gene networks that define functional properties of sensory domains are often explored using non-mammalian vertebrate models, such as the zebrafish. …

Having A High-Activity Catechol-O-Methyltransferase Allele Is Associated With Elevated Anxiety And Lower Salivary Dehydroepiandrosterone But Also Lower Alpha Amylase In Children With Chromosome 22q11.2 Deletion Syndrome., Jessie Beebe

LSU New Orleans Theses and Dissertations

Chromosome 22q11.2 deletion syndrome (22q11.2DS) results from a hemizygous deletion located on the long arm of chromosome 22. The most common deletion sizes affect between 30 and 90 genes. Individuals with 22q11.2DS may develop serious developmental and psychiatric disorders. The phenotype is highly variable, however, and may be influenced by allelic variation of the retained copies of genes covered by the deletion. I set out to examine the effects of two genes, catechol-O-methyltransferase (COMT) and proline dehydrogenase (PRODH), in relation to anxiety in children and adolescents with 22q11.2DS. Individuals with the major COMT allele (higher activity) have significantly higher anxiety …

Biallelic Variants In Pcdhgc4 Cause A Novel Neurodevelopmental Syndrome With Progressive Microcephaly, Seizures, And Joint Anomalies, Maria Iqbal, Reza Maroofian, Büşranur Çavdarlı, Florence Riccardi, Michael Field, Siddharth Banka, Dalal K. Bubshait, Yun Li, Jozef Hertecant, Shahid Mahmood Baig

Department of Biological & Biomedical Sciences

Purpose: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition.
Methods: We performed a detailed clinical characterization of 19 individuals from nine unrelated, consanguineous families with a neurodevelopmental disorder. We used genome/exome sequencing approaches, linkage and cosegregation analyses to identify disease-causing variants, and we performed three-dimensional molecular in silico analysis to predict causality of variants where applicable.
Results: In all affected individuals who presented with a neurodevelopmental syndrome with progressive microcephaly, seizures, and intellectual disability we identified biallelic disease-causing variants in Protocadherin-gamma-C4 (PCDHGC4). Five variants were …

The Neurological Asymmetry Of Self-Face Recognition, Aleksandra Janowska, Brianna Balugas, Matthew Pardillo, Victoria Mistretta, Katherine Chavarria, Janet Brenya, Taylor Shelansky, Vanessa Martinez, Kitty Pagano, Nathira Ahmad, Samantha Zorns, Abigail Straus, Sarah Sierra, Julian Keenan

Department of Biology Faculty Scholarship and Creative Works

While the desire to uncover the neural correlates of consciousness has taken numerous directions, self-face recognition has been a constant in attempts to isolate aspects of self-awareness. The neuroimaging revolution of the 1990s brought about systematic attempts to isolate the underlying neural basis of self-face recognition. These studies, including some of the first fMRI (functional magnetic resonance imaging) examinations, revealed a right-hemisphere bias for self-face recognition in a diverse set of regions including the insula, the dorsal frontal lobe, the temporal parietal junction, and the medial temporal cortex. In this systematic review, we provide confirmation of these data (which are …

The Role Of Placental Genes On Intellectual Disability And Developmental Delay, Maedot A. Yidenk

Dissertations, Theses, and Capstone Projects

The complex interaction between gene expressions and environmental factors plays a key role in the pathogenesis of various diseases, including neurodevelopmental disorders (Lenroot & Giedd, 2008). This study aimed to evaluate first, the magnitude of association between placental gene Methyl-CpG Binding Protein 2 (MeCP2) and intellectual disability (ID) in the offspring and second, the synergy between placental gene Forkhead box protein 1(FOXP1) and developmental delay (DD) in the offspring. We focused on assessing two specific paradigms, i) placental gene expressions of MeCP2 among children that have ID vs. children without ID; and ii) placental gene expression of …

Molecular Characterization Of A Unique Population Of Human Cortical Interneurons; Implications For Primate-Specific Development, Crina Peterson

Biomedical Sciences ETDs

The human brain consists of 86 billion neurons compared to rodent brain, which consists of 75 million neurons, and the underlying mechanisms for the increased complexity of the primate cortex are not fully elucidated. However, an increase in specific cell populations, including calretinin-expressing (CALB2/CR) interneurons (INs), has been identified. In my thesis work, I demonstrate that human pluripotent stem cells (hPSCs) differentiated to neurons by default patterning give rise to this CR population in vitro, providing a method to study their development.

Chapter I reviews cortical development and hPSCs as an appropriate proxy for studying human cortical development. Chapter …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

University Scholar Projects

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

Honors Scholar Theses

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

The Influence Of Autism Linked Gene Topoisomerase 3b (Top3b) On Neural Development In Zebrafish, Sydney Doolittle

Honors College Theses

Autism Spectrum Disorder is a class of developmental disabilities characterized by a spectrum of social, communication, and behavioral impairments in affected individuals. Studies have shown these defects stem from abnormal brain development during critical periods during early development. The underlying genetic cause of these impairments is not well understood but is believed to be a combination of a complex pairing of genetic and environmental factors. One of the genetic factors that has been recognized to influence the phenotypic symptoms of ASD is the enzyme topoisomerase 3β (top3β.) Topoisomerases are responsible for the prevention of supercoiling during DNA replication. Top3β is …

A Pathogenic Ufsp2 Variant In An Autosomal Recessive Form Of Pediatric Neurodevelopmental Anomalies And Epilepsy, Min Ni, Bushra Afroze, Chao Xing, Chunxiao Pan, Yanqiu Shao, Ling Cai, Brandi L. Cantarel, Jimin Pei, Nick V. Grishin, Stacy Hewson

Department of Paediatrics and Child Health

Purpose: Neurodevelopmental disabilities are common and genetically heterogeneous. We identified a homozygous variant in the gene encoding UFM1-specific peptidase 2 (UFSP2), which participates in the UFMylation pathway of protein modification. UFSP2 variants are implicated in autosomal dominant skeletal dysplasias, but not neurodevelopmental disorders. Homozygosity for the variant occurred in eight children from four South Asian families with neurodevelopmental delay and epilepsy. We describe the clinical consequences of this variant and its effect on UFMylation.
Methods: Exome sequencing was used to detect potentially pathogenic variants and identify shared regions of homozygosity. Immunoblotting assessed protein expression and post-translational modifications in patient-derived fibroblasts. …

Estrogen Disruption Of Hypothalamic Neural Activity, Princess Dickson

Cal Poly Humboldt theses and projects

The brain is highly dependent on the endocrine system for proper neurodevelopment, as it plays a key role in many biological processes. Bisphenol A is a chemical found in plastics that has the potential to mimic the effects of Estrogen in the body, at least weakly. People interact with plastic that contains BPA regularly, and people are at risk for exposure even before being born. The abundance of BPA, along with other exogenous estrogens, makes examining the relationship between early exposure and changes in brain activity imperative. The current study aims to establish a relationship between disrupted estrogen function and …

Identification Of De Novo Mutations In Prenatal Neurodevelopment-Associated Genes In Schizophrenia In Two Han Chinese Patient-Sibling Family-Based Cohorts, Shan Jiang, Daizhan Zhou, Yin-Ying Wang, Peilin Jia, Chunling Wan, Xingwang Li, Guang He, Dongmei Cao, Xiaoqian Jiang, Kenneth S. Kendler, Ming Tsuang, Travis Mize, Jain-Shing Wu, Yimei Lu, Lin He, Jingchun Chen, Zhongming Zhao, Xiangning Chen

School of Medicine Faculty Research

Schizophrenia (SCZ) is a severe psychiatric disorder with a strong genetic component. High heritability of SCZ suggests a major role for transmitted genetic variants. Furthermore, SCZ is also associated with a marked reduction in fecundity, leading to the hypothesis that alleles with large effects on risk might often occur de novo. In this study, we conducted whole-genome sequencing for 23 families from two cohorts with unaffected siblings and parents. Two nonsense de novo mutations (DNMs) in GJC1 and HIST1H2AD were identified in SCZ patients. Ten genes (DPYSL2, NBPF1, SDK1, ZNF595, ZNF718, GCNT2, SNX9, AACS, KCNQ1, and MSI2) were found to …

Gene Regulation And Cell Fate Choice In The Developing Vertebrate Retina, Sruti Patoori

Dissertations, Theses, and Capstone Projects

The diverse neuronal cell types in the vertebrate retina all originate from multipotent retinal progenitor cells (RPCs). These undergo a series of molecular changes driven by developmental gene regulatory networks (GRNs) as they divide to generate RPCs which are more restricted in their potential fates. It is crucial to understand these GRNs and changes to gene expression in order to understand how cell identity is established during retinal development. In particular, the GRN that promotes the development of cone photoreceptors and horizontal cells is not well-defined. This work focuses on two approaches to further elucidate the components of this regulatory …

Notch Inhibitors And The Bet Inhibitor Jq-1 Decrease The Growth Of Primary Tumor Cells Derived From A Novel Mouse Model Of C11orf95-Rela Induced Brain Tumor, Ericka Randazzo, Jesse Dunnack, Justin Fang, Joseph Loturco Phd

University Scholar Projects

Brain tumors are the most common childhood solid malignancy, and because of remarkable advances in treating many cancers outside of the brain, they have become the leading cause of cancer mortality in children. Ependymomas are a class of brain tumors which can be further subdivided into three groups based upon their location and genetic features. Of the three classes, supratentorial ependymomas are the only subgroup known to be marked by an oncogenic driver gene, which consists of a fusion mutation between the C11orf95 and RELA genes. C11orf95-RELA positive tumors are the most aggressive and lethal of …

Glial Cell Expansion And Intercellular Signaling In The Developing Medial Nucleus Of The Trapezoid Body (Mntb), Ashley N. Brandebura

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neural circuit formation is a complex process involving coordinated communication between neurons, glia and vascular-associated cells (VACs). Each cell type is responsible for a unique transcriptional and translational contribution to tissue maturation. Deciphering the intercellular signaling patterns which guide neural circuit formation during normal development is thus an essential step in understanding which components of neural circuit formation go awry in neurodevelopmental disorders. The medial nucleus of the trapezoid body (MNTB), located in the auditory brainstem, was used as a model system to study the dynamics of neural circuit formation because it contains a mostly homogeneous population of postsynaptic neurons …

Underlying Contribution Of Executive Functioning To Cognition And Academic Achievement In Individuals With Dystrophinopathy, Robert Fee

Dissertations, Theses, and Capstone Projects

Dystrophinopathy is a genetic disorder that results in the lack of or abnormal expression of the protein dystrophin. It is a disorder that alters cell structure and function, impacts the developing brain and brain function, presents with multi-domain cognitive deficits, and influences both mood and behavior. Cognitive impairments appear to be more localized to specific areas of functioning rather than a global deficit; however, deficits have been identified across multiple cognitive domains including language and aspects of executive functioning. A careful examination of the cognitive phenotype and its association to mutations affecting CNS isoforms is necessary to clarify the neuropsychological …

The Ush2a Gene: An Analysis Of Ultrasonic Vocalizations In A Mouse Model Of Usher Syndrome Type 2, Kiana R. Akhundzadeh

Honors Scholar Theses

Usher syndrome type 2 is a complex autosomal recessive genetic disorder that is characterized by moderate to severe congenital sensorineural hearing loss, the onset of retinitis pigmentosa in the second decade of life, and in some cases, vestibular dysfunction. Mutations in the USH2A gene account for 85% of cases of type 2. The USH2A gene is responsible for encoding the protein usherin, which has an important role in the development and function of inner ear hair cells and retinal photoreceptors. Until recently, it has been believed that carriers of the USH2A mutation were phenotype free. However, recent data has suggested …

Ephrin Receptors, Aiy Interneuron Physiology, And Behavior, Tyler Hill

Master of Science in Integrative Biology Theses

In order to survive, an organism must be able to receive, integrate, and respond to sensory stimuli. However, the cellular basis of sensory perception and response is difficult to study in complex animals such as humans, and is therefore poorly understood. The nematode Caenorhabditis elegans is a relatively simple organism yet displays many distinct behaviors, making it an ideal system to understand the relationship between gene function, cell shape, cell physiology, and behavioral output. Much of the thermosensory and chemosensory information that the nematode receives from its sensory neurons is processed via a pair of interneurons called AIYL and AIYR. …

Modeling 3d Retinogenesis In Mouse Embryonic Stem Cells Following Crispr-Mediated Crx Knockdown, Pooja Prasad

Dissertations, Masters Theses, Capstones, and Culminating Projects

An emerging technology known as three-dimensional (3D) tissue engineering has allowed scientists to mimic tissues found in vivo. Previous studies indicate that it is possible to differentiate dissociated mouse embryonic stem cells (mESCs) into 3D retinal tissues in vitro (Bertacchi, 2015; Eiraku, 2012). The newly differentiated retinal tissues are said to encompass all of the major components found in retinal tissues. The generation of in vitro 3D tissues holds great potential in terms of patient-specific disease modeling. Although various diseases have been well-studied in animal models, there are limitations with regards to patient-specificity. The generation of animal models to study …

The Role Of Daf-19 In Non-Ciliated Neurons: How Is Neural Development Regulated By Different Daf-19 Isoforms?, Zabdiel Ek Vazquez

Lawrence University Honors Projects

A degenerative disease-like phenotype, specifically reduction in synaptic protein levels in adult worms, is correlated with loss-of-function of the only RFX transcription factor gene, daf-19, in C. elegans. This gene encodes four known transcription factor isoforms, two of which are correlated with particular functions. The DAF-19C isoform activates genes responsible for cilia development, while DAF-19M is needed for cilia specification in males. A comparison of the transcriptome of daf-19 null and isogenic wild type adult worms suggests both positive and negative regulation of gene expression is correlated with the presence of DAF-19 proteins. We have assessed DAF-19 regulation …

Role Of Sox11 During Vertebrate Ocular Morphogenesis And Retinal Neurogenesis, Lakshmi Shashidharan Pillai

Theses and Dissertations--Biology

Microphthalmia, anophthalmia, and coloboma (MAC) are distinct abnormalities demonstrating a continuum of developmental eye defects that contribute to 15-20% of blindness and severe vision deficiencies in children worldwide. The genetic etiology of MAC is large, complex and encompasses the whole developmental biology of the eye. Understanding how the eye develops will aid in identifying genes and developmental pathways involved in MAC. Although investigation of the genetic architecture of congenital anomalies is growing exponentially, much work remains to be accomplished to understand the complex, genetically heterogeneous congenital anomalies, which significantly impact childhood vision.

With an interest in elucidating the mechanisms that …